SERUM CLUSTERIN AND VITRONECTIN IN ALCOHOLIC CIRRHOSIS

Clusterin and vitronectin are multifunctional regulatory proteins whic h both serve as complement lysis inhibitors. Previous data have strong ly suggested that serum vitronectin is mainly produced in the liver, w hereas the biosynthetic origin for serum clusterin has not been determ ined. In the present study we aimed to determine the role of the liver in producing these proteins and to evaluate the proteins as possible markers of liver failure. We therefore quantified clusterin and vitron ectin in serum from patients suffering from alcoholic liver cirrhosis (n=83), and in serum-free culture supernatants from the hepatoma cell line HepG2. The median clusterin concentration was 0.20 g/l in cirrhos is and 0.37 g/l in the controls, whereas corresponding vitronectin val ues were 0.19 and 0.26 g/l, respectively. The concentration of both pr oteins showed significant correlation (p<0.0001) with disease severity and with established plasma markers of hepatic synthetic function, su ch as albumin and prothrombin complex. The clusterin level, but not th e vitronectin level, correlated with survival (p=0.005). The rates of synthesis of clusterin, vitronectin and C3 from HepG2 cells were 0.02, 0.21 and 1.9 mu g/10(6) cells/24 h, respectively. From the present da ta we conclude that clusterin (as vitronectin and C3) is mainly produc ed in the liver and may be a useful marker in the evaluation of severi ty of liver disease and prognosis of patients with alcoholic cirrhosis .